Fanconi anemia (FA) is a rare, autosomal recessive genome instability syndrome in which patients are at a dramatically elevated risk of squamous cell carcinoma (SCC) of the head and neck and anogenital tract.
Tumors appear early in life, and progress with striking aggressiveness. Conventional clastogenic therapies such as radiation and chemotherapy are often toxic because of the patients’ DNA damage response defects. Development of alternative treatments has been severely limited by the lack of availability of human models of FA SCC.
The FA Comprehensive Care Center at Cincinnati Children’s Hospital Medical Center has offered a unique opportunity for translational studies, and resulting patient-derived 3-D SCC models will be exploited to facilitate screens for new therapies and support preclinical trials for new treatments.
Our recent data demonstrate that loss of function of the FA pathway in high-risk HPV16 positive keratinocytes stimulates viral and cellular replication in vitro, and malignant transformation in vivo.
Based on these findings, we hypothesize that FA genes are modifiers of HPV infection. Experiments to determine the clinical and molecular importance of FA-HPV crosstalk are currently ongoing.